ArticleMolecular medicine reports2019
High glucose and bupivacaine‑induced cytotoxicity is mediated by enhanced apoptosis and impaired autophagy via the PERK‑ATF4‑CHOP and IRE1‑TRAF2 signaling pathways.
Article in Molecular medicine reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Molecular Mechanisms of Local Anesthetic Toxicity: From Ion Channel Dysregulation to Mitochondrial Dysfunction and Tissue-Specific Injury.International journal of molecular sciences · 2026Review
- Thrombospondin-1 triggers calreticulin expression in human mucoepidermoid carcinoma MC-3 cells via the PERK/CHOP pathway.Oncology letters · 2026Article
- Endoplasmic reticulum stress in skeletal muscle dysfunction of type 2 diabetes: mechanisms and therapeutic implications.Frontiers in endocrinology · 2026Review
- Bupivacaine exacerbates postoperative cognitive dysfunction by suppressing YES1-mediated YAP1 phosphorylation.Experimental brain research · 2025Article
- The Neuroprotective Effects of Primary Functional Components Mulberry Leaf Extract in Diabetes-Induced Oxidative Stress and Inflammation.Journal of agricultural and food chemistry · 2025Article
- Qing Hua Chang Yin ameliorates chronic colitis in mice by inhibiting PERK-ATF4-CHOP pathway of ER stress and the NF-κB signalling pathway.Pharmaceutical biology · 2024Article
- Maternal hyperglycemia inhibits pulmonary vasculogenesis during mouse fetal lung development by promoting GβL Ubiquitination-dependent mammalian target of Rapamycin assembly.Diabetology & metabolic syndrome · 2023Article
- MicroRNA-27a Suppresses the Toxic Action of Mepivacaine on Breast Cancer Cells via Inositol-Requiring Enzyme 1-TNF Receptor-Associated Factor 2.Contrast media & molecular imaging · 2023Article
- Lipid and glucose metabolism in senescence.Frontiers in nutrition · 2023Review
- Hesperidin Protects SH-SY5Y Neuronal Cells against High Glucose-Induced Apoptosis via Regulation of MAPK Signaling.Antioxidants (Basel, Switzerland) · 2022Article
- Involvement of calcium homeostasis and unfolded protein response in autophagy co-induced by molybdenum and cadmium in duck (Anas platyrhyncha) brain.Environmental science and pollution research international · 2022Article
- Subacute cadmium exposure modulates Th1 polarization to trigger ER stress-induced porcine hepatocyte apoptosis via regulation of miR-369-TNFα axis.Environmental science and pollution research international · 2022Article
- New insights into the interplay between autophagy and oxidative and endoplasmic reticulum stress in neuronal cell death and survival.Frontiers in cell and developmental biology · 2022Review
- Protein Kinases Mediate Anti-Inflammatory Effects of Cannabidiol and Estradiol Against High Glucose in Cardiac Sodium Channels.Frontiers in pharmacology · 2021Article
- Maternal sciatic nerve administered bupivacaine induces hippocampal cell apoptosis in offspring.BMC anesthesiology · 2020Article
- Cannabidiol protects against high glucose-induced oxidative stress and cytotoxicity in cardiac voltage-gated sodium channels.British journal of pharmacology · 2020Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bupivacaine has previously been reported to induce neurotoxicity, which is further enhanced by high glucose levels. In the present study, the underlying molecular mechanisms via which bupivacaine induces cytotoxicity under high glucose conditions were investigated in cultured human SH‑SY5Y cells. In order to identify the optimal concentrations of glucose and bupivacaine that induced cytotoxicity, SH‑SY5Y cells were treated with 30‑100 mM glucose and 0.5‑1.0 mM bupivacaine. Based on the dose response experiments, 50 mM glucose and 0.5 mM bupivacaine was used in the present study. The effects that 3‑MA (autophagy inhibitor) and rapamycin (RAPA; autophagy inducer) exerted on cell apoptosis, autophagy and the expression of protein kinase R‑like endoplasmic reticulum kinase (PERK)‑activating transcription factor 4 (ATF4)‑C/EBP‑homologous protein (CHOP) and inositol‑requiring enzyme 1 (IRE1)‑tumor necrosis factor receptor associated factor 2 (TRAF2) signaling proteins were measured in high glucose and bupivacaine‑treated cells. Cell viability was measured using a Cell Counting Kit‑8 assay, cell apoptosis was assessed using flow cytometry, and protein expression was determined using western blot analyses. Compared with the control group, high glucose and bupivacaine significantly increased ATF4, CHOP and caspase‑12 expression, increased apoptosis, and decreased p‑IRE1, TRAF2, LC3‑II/LC3‑I and Beclin1 expression. Promoting autophagy with RAPA partly reversed the high glucose and bupivacaine‑induced changes in p‑PERK, CHOP, TRAF2, Beclin1, caspase‑12 and apoptosis, while inhibiting autophagy with 3‑MA further enhanced the changes in ATF4, CHOP, p‑IRE1, TRAF2 and apoptosis. High glucose and bupivacaine induced cytotoxicity in SH‑SY5Y cells, at least in part, through enhancing cell apoptosis and inhibiting autophagy via the PERK‑ATF4‑CHOP and IRE1‑TRAF2 signaling pathways.
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